Method for pumping fluid in a fluid separation device and related devices and systems

ABSTRACT

In a fluid separation device, fluid supplied to a fluid inlet conduit at an inlet flow rate is split such that a first part of the fluid flows into a first outlet conduit and into a pump at a first flow rate, and a second part of the fluid flows from the fluid inlet conduit into a second outlet conduit at a second flow rate. The second flow rate is controlled by controlling the pump such that, regardless of inlet pressure in the fluid inlet conduit, the first part of the fluid is continuously conducted away from the fluid inlet conduit at a defined value of the first flow rate. The second flow rate is defined based on the defined value of the first flow rate.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.13/441,021, filed Apr. 6, 2012, which claims priority from UK PatentApplication No. GB 1107658.5, filed May 9, 2011, which are incorporatedherein by reference in their entireties.

TECHNICAL FIELD

The present invention relates to a fluid pump, a flow splitter, a sampleseparation device, and methods of handling fluids.

BACKGROUND

US 2008/0022765 discloses a liquid chromatography device, particularly aflow meter with a metering device for intaking and metering anexternally given volume of a fluid, and with a control unit forcontrolling the fluid intake of the metering device for determining aflow rate of the fluid.

In liquid chromatography, a fluidic sample and an eluent (liquid mobilephase) may be pumped through conduits and a column in which separationof sample components takes place. The column may comprise a materialwhich is capable of separating different components of the fluidicanalyte. Such a packing material, so-called beads which may comprisesilica gel, may be filled into a column tube which may be connected toother elements (like a control unit, containers including sample and/orbuffers) by conduits. The composition of the mobile phase can beadjusted by composing the mobile phase from different fluidic componentswith variable contributions. Under undesired circumstances, the flow andsometimes also the composition of the delivered mobile phase may bealtered or disturbed, which may deteriorate proper operation of thesample separation device.

In HPLC technology, a desired flow through a separation column may besignificantly larger than a desired flow through a mass spectroscopydetector which is used for analyzing separated components of the fluid.On the one hand, reducing the flow through the separation column to meetthe requirements of mass spectroscopy may result in artifacts in thedetection peaks such as peak broadening. On the other hand, increasingthe flow through the mass spectroscopy device to meet the requirementsof the separation column is not easily possible as well. Thus, properoperation of a fluid separation device may still be difficultparticularly when a mass spectroscopy device shall be implemented foranalysis purposes.

Therefore, there is a need to efficiently manage flow streams forenabling improved performance of fluid separation.

SUMMARY

To address the foregoing problems, in whole or in part, and/or otherproblems that may have been observed by persons skilled in the art, thepresent disclosure provides methods, processes, systems, apparatus,instruments, and/or devices, as described by way of example inimplementations set forth below.

According to an exemplary embodiment of the present invention, a fluidpump for a fluid separation device for separating a fluid is provided,wherein the fluid pump comprises a fluid inlet being supplyable withfluid with an inlet pressure, and a fluid conducting mechanismconfigured for conducting the fluid supplied to the fluid inlet towardsa connected fluidic path, wherein the fluid conducting mechanism iscontrollable so that, regardless of a value of the inlet pressure, thefluid is continuously conducted away from the fluid inlet with adefinable (or defined) flow rate. It has to be understood that this canbe accomplished as an active pumping action, although in reversedirection, in contrast to passive modes, which modulate the restrictionof a hydraulic path in order to control the rate of flow.

According to another exemplary embodiment, a flow splitter for a fluidseparation device for separating a fluid is provided, wherein the flowsplitter comprises a fluid inlet conduit by which fluid is supplyable, afirst fluid outlet conduit and a second fluid outlet conduit both beingin fluid communication with the fluid inlet conduit so that at least apart of fluid supplied by the fluid inlet conduit is split between thefirst fluid outlet conduit and the second fluid outlet conduit, whereinthe flow splitter is configured so that the portion of the fluidsupplied through the fluid inlet conduit is continuously conducted awayfrom the junction and thus from the first fluid outlet conduit with adefinable (or defined) flow rate. In other terms, a flow subtractionunit can be provided.

According to still another exemplary embodiment, a fluid separationdevice for separating a fluid is provided, wherein the fluid separationdevice comprises a fluid drive, particularly a pumping system,configured to drive the fluid through the fluid separation device, aseparation unit, particularly a chromatographic column, configured forseparating the fluid. Additionally, a fluid pump having theabove-mentioned features and/or a flow splitter having theabove-mentioned features may be provided in the fluid separation device.The fluid pump and/or the flow splitter may be arranged for exampleupstream of the separation unit to operate the pump under its optimalconditions while the separation unit is operated best at a smaller flowrate, or downstream from the separation unit to operate a downstreamdevice, such as detection or post-separation treatment, which runs bestbelow the separation unit's best flow rate.

According to still another exemplary embodiment, a method of pumpingfluid in a fluid separation device for separating the fluid is provided,wherein the method comprises supplying a fluid inlet with the fluid withan inlet pressure, conducting the fluid supplied to the fluid inlet by afluid conducting mechanism towards a connected fluidic path, andcontrolling the fluid conducting mechanism so that, regardless of avalue of the inlet pressure, the fluid is continuously conducted awayfrom the fluid inlet with a defined flow rate.

According to still another exemplary embodiment, a method of splitting afluid flowing in a fluid separation device for separating a fluid isprovided, wherein the method comprises supplying fluid to a fluid inletconduit, splitting at least a part of the fluid supplied by the fluidinlet conduit between a first fluid outlet conduit and a second fluidoutlet conduit both being in fluid communication with the fluid inletconduit, and controlling the fluid flow so that the part of the fluidconducted to the first fluid outlet conduit is continuously conductedaway from the fluid inlet conduit with a defined flow rate.

According to yet another exemplary embodiment, a method of pumping fluidat a variable flow rate in a fluid separation device for separating thefluid is provided, wherein the method comprises supplying a fluid inletwith the fluid at an inlet pressure, conducting the fluid supplied tothe fluid inlet by a fluid conducting mechanism towards a connectedfluidic path, and controlling the fluid conducting mechanism so that,regardless of a value of the inlet pressure, the fluid is continuouslyconducted away from the fluid inlet with an adequate flow rate to leavea constant flow rate for a mass spectroscopy device independent of acolumn flow rate.

According to yet another exemplary embodiment, a method for pumping afluid in a fluid separation device for separating the fluid is provided,wherein the method comprises supplying the fluid to a fluid inletconduit at an inlet flow rate; splitting the fluid supplied to the fluidinlet conduit such that a first part of the fluid flows from the fluidinlet conduit into a first outlet conduit and into a pump inlet of apump at a first flow rate, and a second part of the fluid flows from thefluid inlet conduit into a second outlet conduit at a second flow rate;and controlling the second flow rate of the second part of the fluid, bycontrolling the pump such that, regardless of a value of an inletpressure in the fluid inlet conduit, the first part of the fluid iscontinuously conducted away from the fluid inlet conduit at a definedvalue of the first flow rate, wherein the second flow rate is definedbased on the defined value of the first flow rate.

In the context of this application, the term “inlet pressure” mayparticularly denote an actual pressure value which the fluid pump or theflow splitter is exposed to (or faces) at its fluidic inlet. Hence, thisinlet pressure is the starting point on basis of which the fluid pump orthe flow splitter adjusts its own operation. Whatever the value of theinlet pressure is, the fluid pump or the flow splitter will adjust itsown operation (for instance an internal piston motion and/or a switchingstate of a fluidic valve) so that independently from this actualpressure value, an appropriate fluid flow is set at the fluid inlet tobe intaken.

In the context of this application, the term “continuously conductedaway” may particularly denote that the fluid pump (or the flow splitter)is operable so as to ensure that the flow through the inlet of the fluidpump (or through the first fluid outlet conduit) is controlled, forinstance to be constant or to follow a predefined profile over a certaintime interval, without uncontrollable sub intervals. For instance, thetime interval over which the flow through the inlet is uninterruptedlycontrollable may be larger than one duty cycle, particularly larger thantwo duty cycles, of the fluid pump. For instance, the time interval overwhich the flow through the inlet is uninterruptedly controllable may beparticularly larger than at least twice or at least three times of atime required by a reciprocating piston for moving in a chamber of thefluid pump before changing its motion direction. In contrast toconventional approaches, an exemplary embodiment may allow anuninterrupted definition of the subtracted flow without artifactsarising from an inversion of a motion direction of a reciprocatingpiston at reversal points.

In the context of this application, the terms “definable” and “defined”may particularly denote that it is possible to indicate a target flow tobe subtracted from a fluid inlet interface of the fluid pump. The pumpwill then control its internal operation so as to permanently attain thetarget flow (which may be constant or time-dependent, depending on thedefinition). In an embodiment, the target flow may be “defined” as beingan actually supplied flow (may be measured) minus a given value. Thisway the flow at the said second outlet will be exactly the given value,independent of the level of supplied flow.

In the context of this application, the term “flow rate” mayparticularly denote a fluid volume (or a fluid mass, especially when thefluid is exposed to substantial pressure levels at which compressibilitybecomes noticeable) flowing per time through the fluid inlet or throughthe first fluid outlet conduit.

In the context of this application, the term “flow splitter” mayparticularly denote a fluidic member which is configured for splittingor dividing an inlet flow from a fluid inlet conduit into exactly two ormore than two outlet flows. A flow splitter may provide for a splittingof a source fluid flow into multiple target flows, simply a bifurcationof the flow stream. Examples for a flow splitter are a fluidic T-pieceor a fluidic Y-piece (both having one inlet conduit and two outletconduits) or a fluidic X-piece (having one inlet conduit and threeoutlet conduits, or having two inlet conduits and two outlet conduits).

In the context of this application, the arrangement of a first fluidicmember “downstream” of a second fluidic member in a fluidic path mayparticularly denote that, in a fluid flow direction, the fluid passesfirstly the second fluidic member and subsequently the first fluidicmember. Correspondingly, the arrangement of a first fluidic member“upstream” of a second fluidic member in a fluidic path may particularlydenote that in a fluid flow direction, the fluid passes firstly thefirst fluidic member and later the second fluidic member.

According to an exemplary embodiment, a fluid pump is provided which hasthe characteristic property that independently of a present inletpressure, the fluid pump ensures that, at its fluid inlet, always adefined flow rate is subtracted or intaken. In other words, a preciselydefinable negative flow to be conducted away from the fluid inlet is theparameter which is controlled by the fluid pump. Hence, it can beensured that even in the case of changes of the inlet pressure, thefluid conducting mechanism of the fluid pump will either increase thepower of sucking fluid in its interior or will actively provide acounterforce if the inlet pressure becomes so large that without such anactive counterforce the defined flow rate would be exceeded. Hence, thecontrolled parameter is the flow rate intaken by the fluid pump.

Particularly, this principle or even such a fluid pump may beadvantageously implemented in a flow splitter to allow to subtract adefined flow rate from an inlet flow so that one or more other outletfluid conduits will always carry a flow rate which is, in comparison tothe inlet flow, reduced by the subtracted flow intaken by the fluidpump. Thus, an exceeding flow in the other outlet conduit(s) may beprevented by the fluid pump. At the same time, the other fluid outletconduit(s) will not be influenced at all by this defined flow reductionbecause the fluid pump is not arranged in this or these other fluidoutlet conduit(s) due to the bifurcated structure of the flow splitter.

Such embodiments may be advantageously implemented in a fluid separationdevice such as a HPLC because here it can be desired that the fluidflowing through a separation column should be significantly higher thana flow flowing towards a mass spectroscopy device downstream of thecolumn. By arranging the separation column in the fluid inlet conduit,the fluid pump in the first fluid outlet conduit and the massspectroscopy device in the second fluid outlet conduit, it can becontrolled which fluid flow is subtracted by the fluid pump and willtherefore not be conducted to the mass spectroscopy device.Consequently, the flow through the separation column may be adjusted tobe larger than the flow through the mass spectroscopy device.

For example, flow rates as small as 0.5 ml/min or less can be conductedtowards the mass spectroscopy device, whereas the flow rate at theseparation column may for instance be 2 ml/min or more. Depending onrequired conditions for a certain fluid separation application, anactive splitting which is to be performed by the fluid pump may befine-tuned.

The previously described advantageous effects of flow reduction by adefined intake in a bifurcated fluidic path may be achievedcontinuously, i.e. basically without interruptions. Therefore, anydiscontinuity or unsteadiness of the fluid characteristic which forinstance may conventionally occur at reversal points of reciprocatingpistons of a fluid pump can be prevented by a corresponding operation ofthe fluid pump according to exemplary embodiments.

Next, further exemplary embodiments of the fluid pump will be explained.However, these embodiments also apply to the flow splitter, the fluidseparation device, and the methods.

In an embodiment, the fluid pump comprises a control unit configured forcontrolling the fluid conducting mechanism so that, regardless of thevalue of the inlet pressure, the fluid is continuously conducted awayfrom the fluid inlet with the definable, particularly with a constant,flow rate. Such a control unit may be a central processing unit (CPU) ora microprocessor. It may allow for a self-acting adjustment of theoperation of the fluid pump to meet the given target flow rate, forinstance based on sensor data, library data about solventcharacteristics, calibration data about technical characteristic of thefluid pump or a user input.

In an embodiment, the fluid conducting mechanism is manuallycontrollable by a human user so that, regardless of a value of the inletpressure, the fluid is continuously conducted away from the fluid inletwith the definable, particularly with a constant, flow rate. In thisembodiment, a user himself may control or define the flow rate at thepump inlet which extends the possible applications of the fluid pump tomany technical fields.

In both embodiments, i.e. the adjustment by the control unit or by theuser, it is possible to support the controlling entity with sensormeasurements which may measure parameters such as pressure, flow rate,temperature, etc. at one or various positions of the fluidic system.

In an embodiment, the fluid conducting mechanism is controllable sothat, regardless of the value of the inlet pressure, the fluid iscontinuously conducted away from the fluid inlet with a constant flowrate. A constant flow rate, i.e. a flowing fluid volume per timeinterval which does not change over time, may be advantageous to achievea constant separation performance of a liquid chromatography apparatus.

In an embodiment, the fluid conducting mechanism is controllable so thatwhen the inlet pressure has a value which would (in the absence of thecontrolling) result in a flow rate exceeding the definable flow rate,the fluid conducting mechanism applies a counterforce against the inletpressure so as to adjust the flow rate to the definable flow rate. Thus,the fluid pump may actively fight against a force applied by the fluid.For instance, a piston of the fluid pump may apply a certain pressurecontrary to a flowing direction of the fluid.

In an embodiment, the fluid conducting mechanism is controllable so thatwhen the inlet pressure has a value which would (in the absence of thecontrolling) result in a flow rate below the definable flow rate, thefluid conducting mechanism enforces the inlet pressure by applying anadditional sucking force so as to adjust the flow rate to the definableflow rate. Hence, under operation conditions being inverse to thepreviously mentioned scenario, i.e. a quite small flow rate of thefluid, the fluid pump may actively decrease the inlet pressure byapplying a corresponding enforcing or enhancing additional sucking forceso that the predefined fluid flow is intaken by the fluid pump.

In an embodiment, the fluid conducting mechanism comprises a pistonbeing controllable for reciprocating within a chamber so as to conductthe fluid away from the fluid inlet with the definable flow rate whenmoving rearwardly in the chamber during a part of a duty cycle. In thiscontext, the term “rearwardly” may particularly denote a motion of thepiston within the chamber which is parallel to a motion direction of thestreaming fluid. Therefore, when a piston moves rearwardly, fluid issucked in via the fluid inlet. In contrast to this, a forwardly movingpiston may move antiparallel to the streaming fluid so that a couplingof such a forwardly moving piston and the streaming would not result influid being sucked in the fluid inlet. Therefore, a piston may bedecoupled from the fluid at the fluid inlet during the forward motionand may be coupled to the fluid at the fluid inlet during the backwardmotion. Since a piston in the chamber usually reciprocates, timeintervals of coupling and decoupling the piston with the fluidic inletmay alternate. Particularly, a piston being coupled to the fluid inletclose to a reversal point (i.e. an end position of the piston in thechamber at which it changes from a rearward motion to a forward motion,or vice versa) might cause artifacts in a flow characteristic. Hence, itmay also be possible to couple a piston to the fluid inlet only whenmoving along a central part of the chamber in the rearward direction, sothat the piston may also be fluidically decoupled from the fluid inletwhen travelling in the rearward direction but being sufficiently closeto the end of the chamber.

In an embodiment, the fluid conducting mechanism comprises a furtherpiston being controllable for reciprocating within a further chamber soas to, in cooperation with the previously mentioned piston, conduct thefluid away from the fluid inlet with the definable flow rate when movingrearwardly in the further chamber during a part of the duty cycle.According to such an embodiment, at least two pistons are used whichtogether can ensure the continuous intake of a fluid with a definableflow rate. When the two pistons are operated with a phase differencewith regard to their reciprocation, it can be ensured that there isalways at least one piston moving in a rearward direction so that acontinuous—particularly constant or at least definable (may be rampingor according to a specific shape)—subtracted flow rate is possible.

In an embodiment, any of the piston and the further piston iscontrollable for moving forwardly within the respective chamber during apart of the duty cycle so that, during moving forwardly, a respectivepiston is fluidically disconnected from the fluid inlet. Thus, it can beprevented that the subtracted fluid is reduced by a forwardly movingpiston. However, in case of three or more pistons, it may also bepossible to adjust (for instance reduce) a flow rate by intentionallycoupling also one or more presently forwardly moving pistons to thefluid inlet.

In an embodiment, the fluid pump comprises a switchable fluidic valvehaving fluidic interfaces in fluid communication with the fluid inlet,with the fluidic path, with the chamber and with the further chamber. Inan embodiment, such a switchable valve may be rotary valve. Such arotary valve may be formed of two members or components being rotatablerelative to one another. By taking this measure, it can be possible thatfluid ports formed at certain positions of one of the members of thefluidic valve can be selectively brought in alignment or out ofalignment with grooves formed in the other one of the members of thefluidic valve. Therefore, it is possible to properly define timeintervals during which a respective one of the chambers and pistons iscoupled to the fluid inlet and other time intervals where it isdecoupled from the fluid inlet. The switching logic of the rotary valvemay be configured so that at each time a defined target flow rate issubtracted by the presently fluid coupled pistons from the fluid inlet.

In an embodiment, the fluidic valve is switchable so as to fluidicallydisconnect a respective piston from the fluid inlet upon reversing itsmotion direction from a rearward motion to a forward motion (or apredefined time interval or spatial section before the reversing).According to this embodiment, the piston may be decoupled from the fluidinlet at (or close to) the reversal point of the reciprocating piston,i.e. at top or bottom dead point, so as to prevent artifacts which mayspecifically occur at such a reversal.

In an embodiment, the fluidic valve is switchable so as to fluidicallyconnect a respective piston to the fluid inlet upon reversing its motiondirection from a forward motion to a rearward motion (or a predefinedtime interval or spatial section after the reversing). Therefore, forinstance a predefined delay time after reversing the motion directionfrom forward to rearward motion, the respective piston may be coupled tothe fluid inlet so that it can again contribute to the subtraction ofthe fluid flow over the remaining part of the stroke width.

In an embodiment, the flow rate can be defined to be in a range betweenabout 0.001 ml/min and about 10 ml/min. This is a proper range of flowrates for liquid chromatography applications. However, other flow ratesare possible, especially when the size of pistons is altered (a smallerpiston may correspond to a lower flow, a larger piston may correspond toa higher flow.

In an embodiment, the fluid pump comprises a waste container in fluidcommunication with the fluidic path. Such a waste container may be apressureless container at the end of a fluidic conduit in which fluid(which is for instance no more needed) can be accumulated.

In an embodiment, the fluid conducting mechanism comprises a pluralityof pistons (two, three, or more) each being controllable individuallyfor reciprocating forwardly and rearwardly within a respective chamberto thereby conduct fluid away from the fluid inlet with the definableflow rate. The plurality of pistons may be controlled so that adifference between a sum of displaced fluid volume per time by allpresently rearwardly moving pistons (and being presently in fluidcommunication with the fluid inlet, for instance as a consequence of apresent switching state of the fluidic valve) and a sum of displacedfluid volume per time by all presently forwardly moving pistons (andbeing presently in fluid communication with the fluid inlet, forinstance as a consequence of a present switching state of the fluidicvalve) is constant over time. Thus, the integral forwardly displacedfluidic volume minus the integral backwardly fluid volume can beadjusted to the requirements. Other pistons being presently not in fluidcommunication with the fluid inlet, for instance as a consequence of apresent switching state of the fluidic valve, do not contribute to theadjustment of the actual flow rate.

Next, further exemplary embodiments of the flow splitter will beexplained. However, these embodiments also apply to the fluid pump, thefluid separation device, and the methods.

In an embodiment, a fluid pump (for instance a fluid pump having theabove mentioned features) is arranged in the first fluid outlet conduit.Thus, fluid at exactly the defined flow rate may be sucked into thefirst fluid outlet conduit, so that the flow rate from the fluid inletconduit minus the flow rate in the first fluid outlet conduit may bepumped into the second fluid outlet conduit. Thus, by a manipulation offluid flow in the first fluid outlet conduit, a flow rate in the othersecond fluid outlet conduit may be set without the need to arrange anycontrol member in the second fluid outlet conduit. Hence, the flow inthe second fluid outlet conduit is not disturbed by any control memberin the second fluid outlet conduit.

In an embodiment, the first fluid outlet conduit is fluidically coupledto the fluid inlet of the fluid pump. Thus, the fluid pump mayselectively manipulate the flow condition in the first fluid outletconduit.

In an embodiment, the flow splitter is configured as a fluidic T-pieceor a fluidic Y-piece. Thus, the entire lines of the “T” or “Y” may havean inner lumen, and the crossing point of the lines may be fluidicallycoupled to one another.

In an embodiment, the flow splitter is configured so that the part ofthe fluid conducted to the second fluid outlet conduit is conducted awayfrom the fluid inlet conduit with a flow rate in a range between about0.001 ml/min and about 1 ml/min. However, other adjustable flow ratesare possible, wherein the given range is advantageous for liquidchromatography applications in which a mass spectroscopy device with theneed for small flow rates is arranged in the second fluid outletconduit.

Next, further exemplary embodiments of the fluid separation device willbe explained. However, these embodiments also apply to the fluid pump,the flow splitter, and the methods.

In an embodiment, the fluid pump and/or the flow splitter may bearranged downstream of the separation unit to operate a downstreamdevice, such as detection or post-separation treatment, which runs bestbelow the separation unit's best flow rate.

In an embodiment, the fluid pump and/or the flow splitter may bearranged upstream of the separation unit to operate the pump under itsoptimal conditions while the separation unit it operated best at asmaller flow rate.

In an embodiment, the fluid separation device comprises anelectromagnetic radiation detector configured for detecting theseparated fluid (i.e. different fractions thereof) and being arranged inthe first fluid outlet conduit, i.e. in the same fluid conduit as thefluid pump. Such an electromagnetic radiation detector may be anultraviolet detector having an ultraviolet radiation source and acorresponding detector. Both these components may be part of a flowcell. The separated fluid may be conducted between source and detectorso that the detector can detect electromagnetic radiation afterinteraction with the fluid, for instance measuring absorbance,fluorescence, etc. More generally, the used detector may be based on anelectromagnetic radiation detection principle of any appropriatewavelength, i.e. may detect electromagnetic radiation after interactionwith the fluid, particularly may detect secondary electromagneticradiation coming from the fluid in response to the irradiation of thefluid with primary electromagnetic radiation.

In an embodiment, the electromagnetic radiation detector is arrangedupstream the fluid pump. Hence, the UV detector may be arranged in thesame fluidic path as the fluid pump. By arranging it upstream of thefluid pump, the detection will not be negatively influenced by anyeffects caused by the fluid pump and any influence of the fluid pump onthe fluid so as to obtain reproducible data.

In an embodiment, the fluid separation device comprises a massspectroscopy device configured for analyzing the separated fluid andbeing arranged in the second fluid outlet conduit. Such a massspectroscopy device can be arranged in the other fluid outlet conduit sothat its fluid flow (which is usually quite small) can be defined by thefluid pump in the other parallel fluidic path. Hence, this flow ratecontrol architecture will not negatively influence the operation of themass spectroscopy device or the sample conducted thereto.

In an embodiment, a flow rate of the fluid in the mass spectroscopydevice [[(80)]] is smaller than a flow rate of the fluid in theseparation unit. For instance, it is possible to operate a separationcolumn of a liquid chromatography device with a flow in a range between1 ml/min and 5 ml/min, a flow in an outlet fluid conduit in which a massspectroscopy device is arranged in a range between 0.01 ml/min and 1ml/min. It is also possible to operate the fluid pump to subtract a flowrate (the defined flow rate) in a range between 1 ml/min and 5 ml/min.

The separation unit may be filled with a separating material. Such aseparating material which may also be denoted as a stationary phase maybe any material which allows an adjustable degree of interaction with asample so as to be capable of separating different components of such asample. The separating material may be a liquid chromatography columnfilling material or packing material comprising at least one of thegroup consisting of polystyrene, zeolite, polyvinylalcohol,polytetrafluorethylene, glass, polymeric powder, silicon dioxide, andsilica gel, or any of above with chemically modified (coated, cappedetc) surface. However, any packing material can be used which hasmaterial properties allowing an analyte passing through this material tobe separated into different components, for instance due to differentkinds of interactions or affinities between the packing material andfractions of the analyte.

At least a part of the separation unit may be filled with a fluidseparating material, wherein the fluid separating material may comprisebeads having a size in the range of essentially 0.1 μm to essentially 50μm. Thus, these beads may be small particles which may be filled insidethe separation section of the microfluidic device. The beads may havepores having a size in the range of essentially 0.01 μm to essentially0.2 μm. The fluidic sample may be passed through the pores, wherein aninteraction may occur between the fluidic sample and the pores.

The fluid separation device may be configured for separating componentsof the fluid. When a mobile phase including a fluidic sample passesthrough the fluid separation device, for instance by applying a highpressure, the interaction between a filling of the column and thefluidic sample may allow for separating different components of thesample, as performed in a liquid chromatography device.

However, the fluid separation device may also be configured as a fluidpurification system for purifying the fluidic sample. By spatiallyseparating different fractions of the fluidic sample, a multi-componentsample may be purified, for instance a protein solution. When a proteinsolution has been prepared in a biochemical lab, it may still comprise aplurality of components. If, for instance, only a single protein of thismulti-component liquid is of interest, the sample may be forced to passthe columns. Due to the different interaction of the different proteinfractions with the filling of the column (for instance using a gelelectrophoresis device or a liquid chromatography device), the differentsamples may be distinguished, and one sample or band of material may beselectively isolated as a purified sample.

The sample separation device may be configured to analyze at least onephysical, chemical and/or biological parameter of at least one componentof the mobile phase. The term “physical parameter” may particularlydenote a size or a temperature of the fluid. The term “chemicalparameter” may particularly denote a concentration of a fraction of theanalyte, an affinity parameter, or the like. The term “biologicalparameter” may particularly denote a concentration of a protein, a geneor the like in a biochemical solution, a biological affinity of acomponent, etc.

The fluid separation device may be implemented in different technicalenvironments, like a sensor device, a test device, a device forchemical, biological and/or pharmaceutical analysis, a capillaryelectrophoresis device, a capillary electrochromatography device, aliquid chromatography device, a gas chromatography device, an electronicmeasurement device, or a mass spectroscopy device. Particularly, thefluidic device may be a High Performance Liquid Chromatography device(HPLC) device by which different fractions of an analyte may beseparated, examined and/or analyzed.

The separation unit may be a chromatographic column for separatingcomponents of the fluidic sample. Therefore, exemplary embodiments maybe particularly implemented in the context of a liquid chromatographyapparatus.

The fluid separation device may be configured to conduct a liquid mobilephase through the separation unit and optionally a further separationunit. As an alternative to a liquid mobile phase, a gaseous mobile phaseor a mobile phase including solid particles may be processed using thefluid separation device. Also materials being mixtures of differentphases (solid, liquid, gaseous) may be processed using exemplaryembodiments.

The fluid separation device may be configured to conduct thefluid/mobile phase through the system with a high pressure, particularlyof at least 600 bar, more particularly of at least 1200 bar.

The fluid separation device may be configured as a microfluidic device.The term “microfluidic device” may particularly denote a fluidic deviceas described herein which allows to convey fluid through microchannelshaving a dimension in the order of magnitude of less than 500 μm,particularly less than 200 μm, more particularly less than 100 μm orless than 50 μm or less. The fluid separation device may also beconfigured as a nanofluidic device. The term “nanofluidic device” mayparticularly denote a fluidic device as described herein which allows toconvey fluid through nanochannels having even smaller dimensions thanthe microchannels.

Other devices, apparatus, systems, methods, features and advantages ofthe invention will be or will become apparent to one with skill in theart upon examination of the following figures and detailed description.It is intended that all such additional systems, methods, features andadvantages be included within this description, be within the scope ofthe invention, and be protected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be readily appreciated and become betterunderstood by reference to the following more detailed description ofembodiments in connection with the accompanying drawings. Features thatare substantially or functionally equal or similar will be referred toby the same reference signs.

FIG. 1 illustrates a liquid chromatography system according to anexemplary embodiment.

FIG. 2 shows a more detailed view of a liquid chromatography systemallowing for a quantitative splitting of flow into multiple streams.

FIG. 3 illustrates a flow splitter according to an exemplary embodimentof the invention having a fluid pump according to an exemplaryembodiment of the invention.

FIG. 4 illustrates a fluid pump according to an exemplary embodiment ofthe invention.

FIG. 5A illustrates an operation mode of the fluid pump of FIG. 4, asdescribed herein.

FIG. 5B illustrates another operation mode of the fluid pump of FIG. 4,as described herein.

FIG. 5C illustrates another operation mode of the fluid pump of FIG. 4,as described herein.

FIG. 5D illustrates another operation mode of the fluid pump of FIG. 4,as described herein.

FIG. 5E illustrates another operation mode of the fluid pump of FIG. 4,as described herein.

FIG. 5F illustrates another operation mode of the fluid pump of FIG. 4,as described herein.

FIG. 6 illustrates a fluid pump according to another exemplaryembodiment of the invention.

FIG. 7 illustrates a fluid pump according to another exemplaryembodiment of the invention.

The illustrations in the drawings are schematic.

DETAILED DESCRIPTION

Before describing in detail the drawings, some more general informationwith regard to exemplary embodiments of a flow subtracting pump will begiven. In an embodiment, a reverse operation of a piston pump is used tocontrol a split ratio.

In Liquid Chromatography (LC) systems there is often a requirement tohave both an ultraviolet (or visual light) signal, and a massspectroscopy signal captured at the same time. Modern UHPLC-systemsexhibit high peak capacity, while at the same time they work with lowsample amounts. Compromises are made in multiple aspects to achieveutmost performance.

However, both mentioned detection types (electromagneticradiation-based, mass spectroscopy-based) are different with respect toflow sensitivity and often require their own critical operation set inorder to deliver appropriate performance. While UHPLC is run at higherflow rates, modern mass spectroscopy systems find their optimumsensitivity in lower flow rates. For semi-preparative work a user maylike to collect fractions, which is guided by the MS-signal. The abovementioned detectors may couple downstream of the separation column via aT-piece, which then allows parallel measurements.

According to an exemplary embodiment, the setup is like a normaltwo-detectors-parallel approach. A fluid pump according to an embodimentcan be designed to basically deliver negative flow. For properperformance the fluid pump may be coupled to the outlet of the, forexample, UV-detector, while the mass spectroscopy device is on the otherarm of the T. In order now to have good flow rate on the massspectroscopy arm while the liquid chromatography flow rate it too high,the fluid pump will subtract a controlled amount. Even in case the flowis non-constant the flow towards the mass spectroscopy path can be keptat a constant level by programming the flow subtraction. When recordingthe flow through the fluid pump, even the UV-trace can give exactquantitative information.

Referring now in greater detail to the drawings, FIG. 1 depicts ageneral schematic of a liquid separation system 10. A fluid drive orpump 20 receives a mobile phase from a solvent supply 25, typically viaa degasser 27, which degases and thus reduces the amount of dissolvedgases in the mobile phase. The pump 20—as a mobile phase drive—drivesthe mobile phase through a separating device 30 (such as achromatographic column) comprising a stationary phase. A sampling unit40 can be provided between the pump 20 and the separating device 30 inorder to subject or add (often referred to as sample introduction) asample fluid into the mobile phase. The stationary phase of theseparating device 30 is configured for separating compounds of thesample liquid. A detector 50 is provided for detecting separatedcompounds of the sample fluid. A fractionating unit 60 (or a waste) canbe provided for outputting separated compounds of sample fluid.

While the mobile phase can be comprised of one solvent only, it may alsobe mixed from plural solvents. Such mixing might be a low pressuremixing and provided upstream of the pump 20, so that the pump 20 alreadyreceives and pumps the mixed solvents as the mobile phase.Alternatively, the pump 20 might be comprised of plural individualpumping units, with plural of the pumping units each receiving andpumping a different solvent or mixture, so that the mixing of the mobilephase (as received by the separating device 30) occurs at high pressureand downstream of the pump 20 (or as part thereof). The composition(mixture) of the mobile phase may be kept constant over time, the socalled isocratic mode, or varied over time, the so called gradient mode.

A data processing unit 70, which can be a conventional PC orworkstation, might be coupled (as indicated by the dotted arrows) to oneor more of the devices in the liquid separation system 10 in order toreceive information and/or control operation. For example, the dataprocessing unit 70 might control operation of the pump 20 (e.g. settingcontrol parameters) and receive therefrom information regarding theactual working conditions (such as output pressure, flow rate, etc. atan outlet of the pump). The data processing unit 70 might also controloperation of the solvent supply 25 (e.g. setting the solvent/s orsolvent mixture to be supplied) and/or the degasser 27 (e.g. settingcontrol parameters such as vacuum level) and might receive therefrominformation regarding the actual working conditions (such as solventcomposition supplied over time, flow rate, vacuum level, etc.). The dataprocessing unit 70 might further control operation of the sampling unit40 (e.g. controlling sample injection or synchronizing sample injectionwith operating conditions of the pump 20). The separating device 30might also be controlled by the data processing unit 70 (e.g. selectinga specific flow path or column, setting operation temperature, etc.),and send—in return—information (e.g. operating conditions) to the dataprocessing unit 70. Accordingly, the detector 50 might be controlled bythe data processing unit 70 (e.g. with respect to spectral or wavelengthsettings, setting time constants, start/stop data acquisition), and sendinformation (e.g. about the detected sample compounds) to the dataprocessing unit 70. The data processing unit 70 might also controloperation of the fractionating unit 60 (e.g. in conjunction with datareceived from the detector 50) and provide data back.

As can be taken from FIG. 1, the control unit 70 also controls a fluidpump 90. The fluid pump 90 is arranged downstream of the separationcolumn 30. The fluid pump 90 has a fluid inlet 92 being supplied withseparated fluid at a certain inlet pressure defined by the componentsupstream of a bifurcation point 85. An internal fluid conductionmechanism 94 (described in more detail referring to FIG. 4 and FIG. 5,for instance) of the fluid pump 90 is configured for conducting thefluid supplied to the fluid inlet 92 towards a connected fluidic path 96(from where the fluid is introduced into the fractioner 60 or a wastecontainer) with a defined flow rate of 2.5 ml/min. The fluid conductingmechanism 94 is configured so that, independently of a value of theinlet pressure provided by the pump 20, the fluid is continuouslyintaken in the fluid pump via the fluid inlet 92 with a definable flowrate. The flow rate through the separation column 30 is 3 ml/min.Therefore, by adjusting the flow rate through the fluid inlet 92 to avalue of 2.5 ml/min, it is possible to ensure that the flow rate towardsa fluidic path including a mass spectroscopy device 80 is, in this shownembodiment, 0.5 ml/min. This is highly advantageous because therelatively high flow rate through the separation column 30 allows for ahigh separation performance. On the other hand, the small flow rate of0.5 ml/min meets the specific requirements of the mass spectroscopydevice 80. Therefore, it is possible with the fluid pump 90 (beinglocated in a flow path which differs from the flow path in which theseparation column 30 and the mass spectroscopy device 80 are arranged)to indirectly adjust a flow rate value in the flow path including themass spectroscopy device 80.

FIG. 2 shows another more detailed illustration of the liquidchromatography device 10 of FIG. 1.

As can be taken from FIG. 2 it is possible to mix different solvents,such as an aqueous solvent in a first vial 200 and an organic solvent ina second vial 202 to constitute a mobile phase to be pumped by pump 20.The two solvents in the vials 200, 202 may be mixed after beingconducted through individual pump drives 204 and 206 respectively, whichform a dual pump drive as pump 20. At a mixing T 208, the two solventsare mixed. An injection of a fluidic sample to the mobile phase formedby the two solvents occurs at the autosampler 40 (schematically shown inFIG. 2). A separation column 30 is located downstream the autosampler 40and separates the sample injected into the mobile phase. Afterseparation in the chromatography column 30, the fluid is split atbifurcation point 85 into a first path which connects to a massspectroscopy detection device 80 and into another parallel second pathcoupled to an ultraviolet detector 50 for detecting the separatedfractions of the fluidic sample. A recording computer may be part of thecontrol unit 70.

An arrangement of the fluid pump 90 having fluid inlet 92 and internalfluid conducting mechanism 94 is provided downstream of the ultravioletdetector 50 for defining a defined flow at the fluid inlet 92. Afterhaving left the fluid pump 90, this part of the fluid can be accumulatedin waste container 60. As can be taken from FIG. 2, the fluid pump 90can be realized by two pistons reciprocating within correspondingchambers in combination with a certain fluidic switch. However, thesecomponents will be described in more detail below referring to FIG. 4.

FIG. 3 shows a flow splitter 300 according to an exemplary embodimentwhich can be implemented in the liquid chromatography apparatus 10 shownin FIG. 1 or FIG. 2. However, other applications are possible as well,because the flow splitter 300 is particularly advantageous for allapplications in which a certain fluidic member 350 requires a certainreduced flow rate. Such a fluidic member 350 can be a mass spectroscopydevice, a separation column, a detector, a pump, a sensor or any otherfluidic component which requires or desires that a certain flow rate,particularly a reduced flow rate, flows through this fluidic member 350.

As can be taken from FIG. 3, the flow splitter 300 comprises a fluidinlet conduit 306. Through this fluid inlet conduit 306 a fluid (such asa gas or a liquid) is supplied. This fluid is supplied with an inletflow rate FI. The fluid flowing through the fluid inlet conduit 306 isthen divided or split at a splitting position 360 into a first fluidoutlet conduit 302 and a second fluid outlet conduit 304. However, it isalso possible to provide more than two fluid outlet conduits 302, 304among which the fluid is split. The flow splitter 300 furthermorecomprises a fluid pump 90 in the first fluid outlet conduit 302. Acertain inlet pressure pI is applied to a fluid inlet 92 of the fluidpump 90 by the flowing fluid. The internal construction of the fluidpump 90 is such that independently of the inlet fluid pI, a certain flowrate FT is always subtracted or intaken at the fluid inlet 92.Therefore, the flow rate of fluid flowing through the fluidic member 350is FI-FT. Hence, the fluid pump 90 reduces the flow rate of fluidflowing through the fluidic member 350 as compared to the inlet flowrate FI. By adjusting operation of the fluid pump 90, it is possible toadjust the flow through the fluidic member 350.

FIG. 3 furthermore shows that the control unit 70 controls operation ofthe pump 90, for instance for defining FT or for coordinating thereciprocation of various pistons in an interior thereof. Optionally, itis also possible that an input/output unit 370 is coupled to the controlunit 70 so as to enable a user to provide control instructions or can besupplied with output information. Although not shown in FIG. 3, it ispossible that one or more sensors is or are arranged in the fluidicpath, i.e. in one or multiple of the conduits 306, 304, 302 or 96. Afterhaving left a fluid outlet 98 of the fluid pump 94, the fluid may beconducted into a waste container 308.

FIG. 4 shows a detailed view of the internal construction of a fluidconducting mechanism 94 of the fluid pump 90 according to an exemplaryembodiment of the invention.

As can be shown in FIG. 4, the fluid conducting mechanism 94 comprises afirst piston 400 which is controlled by control unit 70 forreciprocating within a first pump chamber 404 so as to conduct the fluidaway from fluid inlet 92 with a definable flow rate when movingrearwardly in the first chamber 404 during a part of the duty cycle ofthe first piston 400. FIG. 4, as indicated by an arrow 420, shows thefirst piston 400 in an operation mode in which it moves rearwardly.“Rearwardly” means that the fluid entering via fluid inlet 92 and beingconducted through a fluidic valve 408 is flowing basically in parallelto the motion direction of the first piston 400. In contrast to this, aforward operation of the first piston 400 would mean that the pistonmotion is antiparallel to the flow of the fluid which is indicatedschematically by a further arrow 422 (the position of the arrow 422 inFIG. 4 should of course not be understood in a manner that medium flowsinto the piston 400).

Moreover, the fluid conducting mechanism 94 comprises a second piston402 which is controlled by the control unit 70 as well for reciprocatingwithin a separate second pump chamber 406. Therefore, in cooperationwith the first piston 400, the fluid is conducted away continuously fromthe fluid inlet 92 with a definable constant flow rate FT. However, inthe shown embodiment, the second piston 402 is presently not moving sothat it presently does not contribute to intaking a certain fluid flowfrom the fluid inlet 92.

FIG. 4 furthermore schematically illustrates a switchable fluidic valve408 comprising two valve members which are sandwiched perpendicular tothe paper plane of FIG. 4. By rotation, the fluidic valve 408 isswitchable so as to fluidically disconnect a respective piston 400, 402from the fluid inlet 92 when this piston 400, 402 is moving forwardly orupon reversing its motion direction from a rearward motion to a forwardmotion. A fluid intaking performance of a corresponding piston 400 or402 can only be obtained when the piston 400, 402 moves rearwardly.

A presently enabled fluidic path can be defined by the switching stateof the fluidic valve 408 which can be changed by rotating the two valvemembers relative to one another as indicated schematically with afurther arrow 424. One of the two members of the fluidic valve 408 hasmultiple ports 410 (a total of 7 in this case), whereas the other memberof the fluidic valve 408 comprises grooves 426 (two in this case). FIG.4 shows the valve 408 in an operation mode in which a fluidic path isenabled from the fluid inlet 92 through the lower arcuate groove 426towards two ports 410 coupled to the two fluidic chambers 404 and 406,respectively. Furthermore, the fluid may be conducted past therearwardly moving piston 400 towards a respective connected intermediateconduit 432. Correspondingly, an intermediate conduit 434 is providedfor the second chamber 406 as well. Depending on the switching state ofthe fluidic valve 408 the intermediate conduits 432 or 434 may beconnected to a drain conduit 436 from where the corresponding fluid maybe conducted into waste container 308.

In order to obtain a continuous constant flow being subtracted from thefluid inlet 92, the reciprocation of the pistons 400, 402 may becoordinated by the control unit 70 as well as a switching state of thefluidic valve 408. This is performed in such a manner that the sum ofthe fluid flows subtracted by the presently rearwardly reciprocatingpistons 400, 402 (which may be coupled to the fluid inlet 92) meets thedesired defined flow rate value FT. Upon moving forwardly, therespective piston 400, 402 may be decoupled from the fluid inlet 92because in this operation mode the respective piston 400, 402 would notcontribute positively to the subtracting of fluid.

It is also possible that close to a reversal point 444 or 446 of therespective piston 400 or 402, artifacts or discontinuities of theintaken flow rate FT may arise by the respective pistons 400, 402 whichcould deteriorate the constant continuous subtraction of the definedfluid flow. Therefore, it is for instance possible that a certain piston400 or 402 is only connected to the fluid inlet 92 while its fluiddisplacing surface 450 is within a central reciprocating region 448, andsimultaneously providing that the respective other piston 400, 402 ismoving rearwardly.

FIG. 5 again shows the system of FIG. 4 in a simplified illustration,whereas it can be taken from FIG. 5 that there is a constant continuoussubtraction of the flow at the fluid inlet 92.

With regard to the embodiment of FIG. 5, the following describes in moredetail the operation of the system.

The fluid pump 90 is equipped with the rotary valve 408 which isdesigned so the fluid pump 90 can intake liquid from the inlet line 92into two piston pumps in parallel or in either one of them, while theother one is connected to waste. This allows continuous or seamlessintake of fluid of a certain flow rate in either one of the pistons 400,402. The piston movement is controlled by control unit 70 to provide aconstant intake flow, so it is matched to the flow rate of the liquidfed into the fluid pump 90 via the inlet line 92. At any point in timethe total movement of the receiving pistons 400, 402 equals thevolumetric flow rate in the feeding line 92, providing a fast, directand absolute means for maintaining (and if desired determining)volumetric flow.

Due to independent control of the two piston drives together with therotary valve 408 design, the fluid pump 90 is capable of continuouspulsation-free fluid intake. This further improves the operability underdynamic conditions and the precision of the output data and flow ratecontrol.

The fluid pump 90 may be operated in the following operation modes, asshown in FIG. 5:

State IDLE (FIG. 5A): In idle state the rotary valve 408 position issuch that the intake line 92 is connected directly to the waste line 96so the intake stays pressureless.

State INTAKE A (FIG. 5B): When operation is enabled, the valve 408 isrotated to detach the intake line 92 from the waste line 96 and connectit to both pistons 400, 402 simultaneously. The left piston 400 is thenslowly retracted to keep the intake flow rate.

State INTAKE A END/B BEGIN (FIG. 5C): As the left piston 400 approachesits rearmost position, it is decelerated until it comes to halt, whilethe right piston 402 is accelerated synchronously.

State EJECT A/INTAKE B (FIG. 5D): The valve 408 is now rotated to keepthe right piston 402 connected to intake 92, while the left piston 400is detached from intake 92 and connected to the waste line 96. Thecontent of the left piston 400 is now ejected into waste 96. Whenfinished, the valve 408 is rotated back to its previous positionconnecting both pistons 400, 402 to intake.

State INTAKE B END/A BEGIN (FIG. 5E): As the right piston 402 approachesits rearmost position, it is decelerated until it comes to halt, whilethe left piston 400 is accelerated synchronously.

State INTAKE A/EJECT B (FIG. 5F): The valve 408 is rotated to keep theleft piston 400 connected to intake 92, detach the right piston 402 andconnect it to waste 96. After ejecting the right piston 402 into waste,the valve 408 is rotated to its previous position connecting bothpistons 400, 402 to intake.

The scheme of FIG. 5A to FIG. 5F shows that, in an active state of thefluid pump 90, either one of the pistons 400, 402 sucks fluid from theinlet line 92 (first piston 400 in FIG. 5F, second piston 402 in FIG.5D) or both pistons 400, 402 suck fluid from the inlet line 92 (FIG. 5C,FIG. 5E). The former scenario applies when one of the pistons 400, 402presently moves forwardly and therefore is currently disconnected fromthe fluid inlet 92 (first piston 400 in FIG. 5D, second piston 402 inFIG. 5F), the latter scenario applies when both pistons 400, 402presently move rearwardly. When one of the pistons 400, 402 presentlymoves forwardly, its content is drained towards the drain line 96. So itcan be ensured that the fluid flow subtracted via fluid inlet 92 iscontinuously and uninterruptedly the same (or more generally: iscontinuously maintained at a desired value).

The fluid pump 90 may be equipped with high precision SSiC pistons andball screw drives, driven by brushless DC motors which are field vectorcontrolled by a 20 kHz control loop run on a specific processor in aFPGA on a main board.

FIG. 6 illustrates a fluid pump 600 according to another exemplaryembodiment of the invention.

FIG. 6 comprises three pistons 400 in corresponding chambers 404 andalso involves three different valves 602, 604, 606 each being switchableindependently under the control of the control unit 70. In therespective drain lines 96, additional valves may be provided (not shown)so as to allow to close the drain lines 96. In the present operationmode shown in FIG. 6, valve 602 is open since the corresponding piston400 is moving rearwardly. The second valve 604 is presently switchedfrom an on-state to an off-state because the corresponding piston 400 isclose to the reversal point, i.e. the upper dead point. The third valve606 is presently off since the corresponding piston 400 moves forwardly.

FIG. 7 shows still another exemplary embodiment of a fluid pump 700 inwhich two switchable valves 408 are switched by a control unit 70,wherein each of the valves 408 operates two piston chamber pairs 400,404. Again, as in FIG. 6, in the respective drain lines 96, additionalvalves may be provided (not shown) so as to allow to close the drainlines 96.

It should be noted that the term “comprising” does not exclude otherelements or features and the term “a” or “an” does not exclude aplurality. Also elements described in association with differentembodiments may be combined. It should also be noted that referencesigns in the claims shall not be construed as limiting the scope of theclaims.

It will be understood that various aspects or details of the inventionmay be changed without departing from the scope of the invention.Furthermore, the foregoing description is for the purpose ofillustration only, and not for the purpose of limitation—the inventionbeing defined by the claims.

What is claimed is:
 1. A method for pumping a fluid in a fluidseparation device for separating the fluid, the method comprising:supplying the fluid to a fluid inlet conduit at an inlet flow rate;splitting the fluid supplied to the fluid inlet conduit such that afirst part of the fluid flows from the fluid inlet conduit into a firstoutlet conduit and into a pump inlet of a pump at a first flow rate, anda second part of the fluid flows from the fluid inlet conduit into asecond outlet conduit at a second flow rate; and controlling the secondflow rate of the second part of the fluid, by controlling the pump suchthat, regardless of a value of an inlet pressure in the fluid inletconduit, the first part of the fluid is continuously conducted away fromthe fluid inlet conduit at a defined value of the first flow rate,wherein the second flow rate is defined based on the defined value ofthe first flow rate.
 2. The method of claim 1, comprising at least oneof: controlling the pump such that the second flow rate is maintained ata constant value, or according to a predefined profile, over a desiredtime interval; controlling the pump such that the second flow rate ismaintained at a constant value, or according to a predefined profile,over a desired time interval that is larger than one duty cycle of thepump.
 3. The method of claim 1, comprising at least one of: controllingthe pump such that the second flow rate is reduced relative to the inletflow rate by the defined value; controlling the pump such that thesecond flow rate is in a range between 0.01 ml/min and 1 ml/min.
 4. Themethod of claim 1, wherein supplying the fluid to the fluid inletconduit comprises outputting the fluid from a separation unit configuredfor separating the fluid.
 5. The method of claim 4, comprising detectingthe separated fluid in the first outlet conduit upstream of the pumpinlet.
 6. The method of claim 1, wherein controlling the pump comprisesadjusting the pump based on the inlet pressure to maintain the firstflow rate at the defined value.
 7. The method of claim 1, wherein thepump comprises a first chamber communicating with the pump inlet, asecond chamber communicating with the pump inlet, a first piston, and asecond piston, and controlling the pump comprises controllingreciprocation of the first piston in the first chamber and reciprocationof the second piston in the second chamber.
 8. The method of claim 7,wherein controlling the pump comprises at least one of: selectivelyconnecting and disconnecting the first chamber and the second chamberfrom the pump inlet; selectively connecting and disconnecting the firstchamber and the second chamber from a pump outlet of the pump.
 9. Themethod of claim 7, wherein controlling the pump comprises switching afluidic valve of the pump to perform at least one of: selectivelyconnecting and disconnecting the first chamber and the second chamberfrom the pump inlet; selectively connecting and disconnecting the firstchamber and the second chamber from a pump outlet of the pump.
 10. Themethod of claim 7, wherein controlling the pump comprises controllingthe reciprocation of the first piston and the second pistoncooperatively to conduct the first part of the fluid away from the fluidinlet when the first piston is moving rearwardly in the first chamberand when the second piston is moving rearwardly in the second chamber.11. The method of claim 10, wherein controlling the pump comprisescontrolling a fluidic valve switchable to selectively connect the firstchamber to the first inlet and selectively connect the second chamber tothe first inlet.
 12. The method of claim 11, wherein controlling thepump comprises controlling the fluidic valve to connect the firstchamber to the first inlet when the first piston reverses direction frommoving forwardly to moving rearwardly, and to connect the second chamberto the first inlet when the second piston reverses direction from movingforwardly to moving rearwardly.
 13. The method of claim 10, whereincontrolling the pump comprises controlling the reciprocation of thefirst piston and the second piston such that the first piston isdisconnected from the fluid inlet while the first piston is movingforwardly in the first chamber, and the second piston is disconnectedfrom the fluid inlet while the second piston is moving forwardly in thesecond chamber.
 14. The method of claim 13, wherein controlling the pumpcomprises controlling a fluidic valve switchable to selectivelydisconnect the first chamber to from the first inlet and selectivelydisconnect the second chamber from the first inlet.
 15. The method ofclaim 14, wherein controlling the pump comprises controlling the fluidicvalve to disconnect the first chamber from the first inlet when thefirst piston reverses direction from moving rearwardly to movingforwardly, and to disconnect the second chamber from the first inletwhen the second piston reverses direction from moving rearwardly tomoving forwardly.
 16. The method of claim 1, wherein the pump comprisesa plurality of pistons each being controllable for reciprocatingforwardly and rearwardly within a respective chamber to thereby conductfluid away from the fluid inlet with the definable flow rate (FT),wherein the plurality of pistons are controlled so that: a sum ofdisplaced fluid volume per time by all presently rearwardly movingpistons being in fluid communication with the fluid inlet, minus a sumof displaced fluid volume per time by all presently forwardly movingpistons being in fluid communication with the fluid inlet, is constantover time.
 17. The method of claim 1, comprising conducting the secondpart of the fluid at the second flow rate toward a fluidic membercommunicating with the second outlet conduit.
 18. The method of claim17, wherein the fluidic member has a desired flow rate, and controllingthe pump comprises controlling the defined value of the first flow ratesuch that the second flow rate equals the desired flow rate.
 19. Themethod of claim 17, comprising at least one of: the fluidic membercomprises a mass spectroscopy device and the separation unit comprises achromatography device; the fluidic member is selected from the groupconsisting of: a detector device; a device for chemical, biologicaland/or pharmaceutical analysis; a capillary electrophoresis device; aliquid chromatography device; an HPLC device; a gas chromatographydevice; a gel electrophoresis device; a mass spectroscopy device; aanother pump; a sensor; and a combination of two or more of theforegoing.
 20. The method of claim 17, comprising operating the fluidicmember to analyze at least a portion of the second part of the fluid.